The present invention relates to a method for regional blood flow measurement. It further relates to a probe for making such measurements.
Assessment of regional blood flow (RBF) of various organs, i.e., of the volume of blood perfusing a unit volume of tissue per unit of time, has both clinical and physiological significance. Many methods, optical, thermal, acoustical, electrical, radioactive and other were developed for RBF measurements but their clinical application is still limited. Most of the methods provide only qualitative results, while transient clearance methods, which can assess RBF quantitatively with no need for in-vivo calibration, are, in general, hazardous. In transient clearance methods some dilutant is administered to the investigated tissue, either by inhalation or by injection, and RBF is derived from the dependence of the dilutant concentration on time. The commonly used dilutant is either 133Xe or H2. Both materials are hazardous when administered by inhalation, while their injection into the investigated tissue interferes with blood flow.
The relative convenience of thermal measurement has motivated several attempts to evaluate RBF by thermal methods, using the wellknown function of the blood: transferring deep-body heat to the environment. Direct measurement of the temperature of uncovered tissue provides some information on tissue blood flow, which is one of the factors determining tissue temperature. However, this information is only qualitative, since tissue temperature depends also on many other parameters such as tissue conductivity, evaporation rate, radiation and air convection. Direct temperature measurements are valuable only for qualitative comparison of adjacent tissue surfaces, as is done in thermography.
Heat clearance measurements are more directly related to blood flow itself. Many steady-state heat clearance methods--invasive and non-invasive, constant-power or isothermal--have been developed in the last fifty years, with various degrees of success. Analysis of the steady-state methods reveals however, that the amount of heat dissipation by blood flow depends also on the probe geometry as well as on tissue conductivity, necessitating in-vivo calibration in order to obtain quantitative results.
Recently, preliminary results were disclosed of a transient thermal clearance method, in which the dilutant is (negative) heat. A metal plate, thermally insulated from its surroundings, is attached to the investigated tissue, and its temperature is measured by means of a copper-constantan thermocouple embedded in it. The plate temperature is increased towards an equilibrium temperature which, under conditions of perfect thermal insulation, equals the local arterial blood temperature. The rate of heat transfer to the tissue surface depends both on tissue thermal conduction and on heat convection by blood. However, after enough time has elapsed and temperature gradients have been decreased, the main contribution to heat transfer is due to heat convection by blood. At this tage, surface temperature (and the metal plate temperature) is an exponential function of time. Plotting .DELTA.T, the difference between instantanous plate temperature and equilibrium temperature as a function of time on a semi-logarithmic scale, provides a straight line from whose slope, the time constant .tau. of the .DELTA.T-against-time curve, can be derived. The aimed-for regional blood flow F is merely the reciprocal of .tau.. Because of the high values of the time constant (generally 100-600 secons) the final equilibrium temperature T.sub.b is achieved only after 5-25 minutes. When an organ with pathologic blood flow is examined, measurement time may be even longer. The main drawback of the known transient thermal clearance method is its long measurement time. Besides the inconvenience accompanying clinical measurements of long duration, the possible changes in regional blood flow during the long time of measurement interferes with the measurement and reduces its accuracy. Since fluctuations in skin blood flow are a common phenomenon, a severe limitation to the potential applications of the method is inevitable.
The long measurement time of the known transient thermal clearance method is mainly due to the need for determining T.sub.b, the final equilibrium temperature. Since the known method is based on calculating the slope of the curve of .DELTA.T(=T-T.sub.b) against time, it is necessary to obtain the equilibrium temperature T.sub.b. As was noted earlier, this requires much time, especially with low regional blood flow.
Measurement time is further increased due to the fact that the rate of temperature increase at the beginning of measurement does not provide quantitative information about blood flow. This is because heat transfer during this period is substantially influenced by tissue heat conduction. According to the known thermal clearance method, application of (negative) heat is effected by the attachment of a metal plate at room temperature, which results in appreciable temperature gradients in the tissue and high contribution of thermal conduction to heat transfer. Thus, the unproductive first phase of measurement is prolonged, and more time has to elapse until one may assume that a condition of small temperature gradients has been obtained. A solution to the problem may be a probe with means to cool its metal plate and the tissue underneath continuously when attached to the skin. Moderate cooling for long periods of time will result in thermal gradients which for the same average reduction of tissue temperature, are smaller than those obtained by abrupt cooling at lower temperatures. In previous experiments, continuous moderate cooling was effected by water flowing through a polyethylene tube, which was attached to the metal plate. Although results showed an appreciable reduction in the first phase of conductive temperature increase, the heat capacity of the tube and the remaining water interfered with the results.
While the main disadvantage of the known method resided in the need, explained above, to continue the test until the equilibrium temperature T.sub.b has been established, the known probe, which consisted of a metal disk mounted along its entire periphery in a teflon housing, aggravated and added to, this disadvantage in that it undermined the basic assumption of the transient thermal clearance method, according to which all the heat transfered by the blood goes towards heating the tissue and the metal plate. As it turned out, the known probe leaks heat from the metal plate to the housing in two ways: by heat conduction from the relatively large peripheral area of contact with the housing, and by radiation, through the air gap between them, from the back of the plate to the housing walls, the material of which, teflon, was found to be less of an efficient thermal insulation than was originally assumed. These heat losses, besides interfering with the measurement (especially when organs of low regional blood flow are investigated), also prolong measurement time, since more time has to elapse until the metal plate reaches its equilibrium temperature. Moreover, heat leakage is higher during the beginning of the measurement (when thermal gradients between the metal plate and the capsule are higher), thereby increasing deviation of the .DELTA.T vs. time curve from the exponential. Thus, the appropriate instant for blood flow measurements is further delayed.
It is one of the objects of the present invention to overcome the above-mentioned difficulties and drawbacks of the prior-art methods for regional blood-flow measurements, and to propose a method that is inherently safe, gives accurate results even with low regional blood flows, and does not require the attainment of equilibrium temperature T.sub.b.